Inhibitory Effect of Dihydroartemisinin on the Proliferation and Migration of Melanoma Cells and Experimental Lung Metastasis From Melanoma in Mice

Abstract

Melanoma is aggressive and can metastasize in the early stage of tumor. It has been proved that dihydroartemisinin (DHA) positively affects the treatment of tumors and has no apparent toxic and side effects. Our previous research has shown that DHA can suppress the formation of melanoma. However, it remains poorly established how DHA impacts the invasion and metastasis of melanoma. In this study, B16F10 and A375 cell lines and metastatic tumor models will be used to investigate the effects of DHA. The present results demonstrated that DHA inhibited the proliferative capacity in A375 and B16F10 cells. As expected, the migration capacity of A375 and B16F10 cells was also reduced after DHA administration. DHA alleviated the severity and histopathological changes of melanoma in mice. DHA induced expansion of CD8+CTL in the tumor microenvironment. By contrast, DHA inhibited Treg cells infiltration into the tumor microenvironment. DHA enhanced apoptosis of melanoma by regulating FasL expression and Granzyme B secretion in CD8+CTLs. Moreover, DHA impacts STAT3-induced EMT and MMPS in tumor tissue. Furthermore, Metabolomics analysis indicated that PGD2 and EPA significantly increased after DHA administration. In conclusion, DHA inhibited the proliferation, migration and metastasis of melanoma in vitro and in vivo. These results have important implications for the potential use of DHA in the treatment of melanoma in humans.

Development of a Macrophage-Related Risk Model for Metastatic Melanoma

“…The most optimal therapeutic strategy is considered to involve integrating most of the immune subpopulations without causing significant toxicity. In our previous study, we found that CD8 + CTL cells were effective at inducing the apoptosis of melanoma cells in mice with metastatic cancer, as inhibition of the immunosuppressive effect of the Treg cell can impress melanoma in situ [ 5 , 6 ]. It has been demonstrated that M1 macrophages expressed high levels of CD86, MHC II and B7 and mediated anti-tumor effects by secreting high-level cytokines (such as IL-12, IL-23, IL-1 and IL-6) and chemokines (MCP-1, CCL3, CXCL9, CXCL10, etc.)…”

A network pharmacology approach to evaluate the synergistic effect of dihydromyricetin and myricitrin in vine tea on the proliferation of B16F10 cells

“…However, surgical resection is limited and cannot effectively treat metastatic tumors. Radiotherapy and chemotherapy have drug toxicity and a high cost (5,6). Therefore, it is important to prevent melanoma through lifestyle.…”